Center for NanoBiotechnology Research (CNBR), Alabama State University, Montgomery, AL, USA.
Department of Public Health Sciences, Pennsylvania State University College of Medicine, Hershey, PA, USA.
Int J Nanomedicine. 2024 Feb 8;19:1287-1301. doi: 10.2147/IJN.S432970. eCollection 2024.
Interleukin-10 (IL-10) is a key anti-inflammatory mediator in protecting host from over-exuberant responses to pathogens and play important roles in wound healing, autoimmunity, cancer, and homeostasis. However, its application as a therapeutic agent for biomedical applications has been limited due to its short biological half-life. Therefore, it is important to prolong the half-life of IL-10 to replace the current therapeutic application, which relies on administering large and repeated dosages. Therefore, not a cost-effective approach. Thus, studies that aim to address this type of challenges are always in need.
Recombinant IL-10 was encapsulated in biodegradable nanoparticles (Poly-(Lactic-co-Glycolic Acid) and Chitosan)) by the double emulsion method and then characterized for size, surface charge, thermal stability, cytotoxicity, in vitro release, UV-visible spectroscopy, and Fourier Transform-Infrared Spectroscopy as well as evaluated for its anti-inflammatory effects. Bioactivity of encapsulated IL-10 was evaluated in vitro using J774A.1 macrophage cell-line and in vivo using BALB/c mice. Inflammatory cytokines (IL-6 and TNF-α) were quantified from culture supernatants using specific enzyme-linked immunosorbent assay (ELISA), and significance was analyzed using ANOVA.
We obtained a high 96% encapsulation efficiency with smooth encapsulated IL-10 nanoparticles of ~100-150 nm size and release from nanoparticles as measurable to 22 days. Our result demonstrated that encapsulated IL-10 was biocompatible and functional by reducing the inflammatory responses induced by LPS in macrophages. Of significance, we also proved the functionality of encapsulated IL-10 by its capacity to reduce inflammation in BALB/c mice as provoked by , an inflammatory sexually transmitted infectious bacterium.
Collectively, our results show the successful IL-10 encapsulation, slow release to prolong its biological half-life and reduce inflammatory cytokines IL-6 and TNF production in vitro and in mice. Our results serve as proof of concept to further explore the therapeutic prospective of encapsulated IL-10 for biomedical applications, including inflammatory diseases.
白细胞介素-10(IL-10)是一种关键的抗炎介质,可保护宿主免受病原体过度反应的影响,并在伤口愈合、自身免疫、癌症和体内平衡中发挥重要作用。然而,由于其生物学半衰期短,其作为生物医学应用的治疗剂的应用受到限制。因此,延长 IL-10 的半衰期以替代当前依赖于大剂量和重复剂量的治疗应用非常重要。因此,这不是一种具有成本效益的方法。因此,总是需要研究旨在解决此类挑战的方法。
通过复乳法将重组白细胞介素-10 包封在可生物降解的纳米颗粒(聚(乳酸-共-乙醇酸)和壳聚糖)中,然后对其大小、表面电荷、热稳定性、细胞毒性、体外释放、紫外可见光谱和傅里叶变换-红外光谱进行表征,并评估其抗炎作用。使用 J774A.1 巨噬细胞系在体外和 BALB/c 小鼠在体内评估包封的白细胞介素-10 的生物活性。使用特定的酶联免疫吸附测定(ELISA)从培养上清液中定量炎性细胞因子(IL-6 和 TNF-α),并使用 ANOVA 分析其显著性。
我们获得了 96%的高包封效率,得到了~100-150nm 大小的光滑包封的白细胞介素-10 纳米颗粒,从纳米颗粒中的释放可测量到 22 天。我们的结果表明,包封的白细胞介素-10 通过减少 LPS 在巨噬细胞中诱导的炎症反应而具有生物相容性和功能。值得注意的是,我们还通过其降低由炎症性性传播感染细菌引起的 BALB/c 小鼠炎症的能力证明了包封的白细胞介素-10 的功能。
总的来说,我们的结果表明成功地对白细胞介素-10 进行了包封,缓慢释放以延长其生物学半衰期,并减少了体外和小鼠体内的炎症细胞因子 IL-6 和 TNF 的产生。我们的结果为进一步探索包封白细胞介素-10 用于生物医学应用(包括炎症性疾病)的治疗前景提供了依据。